Patterns of C-reactive protein trends during clozapine titration and the onset of clozapine-induced inflammation: a case series of weekly and daily C-reactive protein monitoring

BackgroundInternational guidelines for clozapine titration recommend measuring C-reactive protein (CRP) weekly for 4 weeks after clozapine initiation to prevent fatal inflammatory adverse events, including myocarditis. However, limited evidence exists regarding whether weekly CRP monitoring can prevent clozapine-induced inflammation.AimsWe examined the relationship between CRP trends and the development of clozapine-induced inflammation. We also explored the usefulness and limitations of CRP monitoring during clozapine titration.MethodThis study presents 17 and 4 cases of weekly and daily CRP monitoring during clozapine initiation, respectively.ResultsAmong 17 patients with weekly CRP measurements, 7 had fever. Elevated CRP levels were detected before the onset of fever in two of the seven patients. Of the five remaining patients, the CRP levels on a previous test had been low; however, the fever developed suddenly. Of the 10 patients with no fever under weekly CRP monitoring, three had elevated CRP levels >3.0 mg/dL. Refraining from increasing the clozapine dose may have prevented fever in these patients. Among four patients with daily CRP measurements, two became febrile. In both cases, CRP levels increased almost simultaneously with the onset of fever.ConclusionWeekly and daily CRP monitoring during clozapine titration is valuable for preventing clozapine-induced inflammation, assessing its severity, and guiding clozapine dose adjustments. Weekly CRP monitoring may not adequately predict clozapine-induced inflammation in some cases. Consequently, clinicians should be aware of the sudden onset of clozapine-induced inflammation, even if CRP levels are low. Daily CRP monitoring is better for detecting clozapine-induced inflammation

Differences in Ocular Complications Between Candida albicans and Non-albicans Candida Infection Analyzed by Epidemiology and a Mouse Ocular Candidiasis Model

Objectives:Candida species are a major cause of hospital infections, including ocular candidiasis, but few studies have examined the propensities of specific species to invade the eye or the unique immunological responses induced. This study examined the frequency and characteristics of species-specific Candida eye infections by epidemiology and experiments using a mouse ocular candidiasis model.Methods: We reviewed medical records of candidemia patients from January 2012 to March 2017. We also evaluated ocular fungal burden, inflammatory cytokine and chemokine profiles, and inflammatory cell profiles in mice infected with Candida albicans, Candida glabrata, or Candida parapsilosis.Results: During the study period, 20 ocular candidiasis cases were diagnosed among 99 candidemia patients examined by ophthalmologists. Although C. parapsilosis was the most frequent candidemia pathogen, only C. albicans infection was significantly associated with ocular candidiasis by multivariate analysis. In mice, ocular fungal burden and inflammatory mediators were significantly higher during C. albicans infection, and histopathological analysis revealed invading C. albicans surrounded by inflammatory cells. Ocular neutrophil and inflammatory monocyte numbers were significantly greater during C. albicans infection.Conclusion:Candida albicans is strongly associated with ocular candidiasis due to greater capacity for invasion, induction of inflammatory mediators, and recruitment of neutrophils and inflammatory monocytes

Camellia_SSR_data_GenAlEx

The microsatellite data of the Japanese camellia in the GenAlEx format

Weevil_COI_data_Arlequin

The mitochondrial COI data of the camellia weevil in the Arlequin format

Morphology_Climate_data

Study sites, Morphological data and climatic conditions of the study sites

Migrate_infile_Weevil

The weevil mt COI data for the Migrate-n analysis

Data from: Metapopulation structure of a seed-predator weevil and its host plants in arms race coevolution

Although the importance of gene flow in the geographic structuring of host–parasite interactions has been well discussed, little is known about how dispersal drives the spatial dynamics of other types of coevolutionary interactions in nature. We evaluated the roles of gene flow in the geographically structured processes of a predator–prey arms race involving a seed-predatory weevil with a long mouthpart and its host camellia plant with a thick fruit coat. Molecular genetic analyses showed that both weevil and camellia populations were structured at a spatial scale of several kilometers. Importantly, the spatial pattern of the migration of weevils, but not that of camellias, imposed significant effects on the geographic configuration of the levels of coevolutionary escalation. This result suggests that even if migration is limited in one species (camellia), local coevolution with the other species that migrates between neighboring localities (weevil) can reduce the inter-population difference in the local adaptive optima of the former species. Thus, gene flow of a species potentially homogenizes local biological environments provided by the species and thereby promotes the evolutionary convergence of its coevolving counterparts. Consequently, by focusing on coevolutionary interactions in natural communities, “indirect” effects of gene flow on the adaptive divergence of organisms could be identified

Toju_AmNat_MS52288

The data used for the statistical analysis of each figure/table are shown in each excel sheet

Migrate_infile_Weevil

The weevil mt COI data for the Migrate-n analysis